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Calpain-mediated TBP cleavage disturbs neuronal AMOT-YAP1 signalling.
Nature Communications · · Journal Article · Open access
Incebacak Eltemur, Fath + more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
Calpain cleavage of neuronal TBP at T106 generates polyglutamine-containing fragments that mislocalize and aggregate, linked to AMOT-YAP1 signalling disruption in SCA17 models.
- Why it matters: TBP dysfunction in spinocerebellar ataxia type 17 remains mechanistically unclear, and prior work implicated calpains without identifying downstream neuronal signalling pathways.
- What they did: The study mapped a major calpain cleavage site after residue T106 and used SCA17 cell line multi-omics, then tested AMOT function across SCA17 cell lines, patient-derived fibroblasts, induced neurons, and rat and zebrafish models.
- The result: TBP fragments altered neuronal and neurodegeneration pathways, identifying AMOT as key, and experiments confirmed AMOT’s pivotal role in neurons via YAP1-dependent signalling.
The findingWhy it mattersWhat they didThe result
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